FEATURE: The drugs don't work – but engineering could hold the answer

Drug-resistant bacteria could kill millions. Can engineering come to the rescue?

Since Alexander Fleming discovered penicillin in 1928, antibiotics have saved millions – maybe billions – of lives. But they are getting less effective.

Random mutations in the genetic code of bacteria imbue some of them with resistance to antibiotics. They survive, thrive, and pass on their drug-resistant DNA to their descendants. This is anti-microbial resistance, and it’s becoming a big problem.

In 1945, when Fleming collected his Nobel Prize, he warned that resistance would happen, and would kill people. But for decades we were remarkably carefree in our use of antibiotics.

We pumped them into our farm animals, and allowed them to leach into rivers and streams. Harried doctors overprescribed them to everyone with a tickle in their throat. Patients would pass unused pills onto family members or fail to finish their courses of tablets, so creating a fertile breeding ground for ‘superbugs’ that don’t respond to anything in our antibiotics arsenal.

Today, by conservative estimates, drug-resistant infections kill one person every 45 seconds. By 2050 that figure could rise to one death every three seconds, according to a talk by England’s chief medical officer Dame Sally Davies, at the 2017 Global Grand Challenges Summit in Washington DC.

Usually, when one antibiotic doesn’t work, doctors simply switch to another one. But, as Davies pointed out, it has been more than 30 years since a new class of antibiotic reached patients. “Bugs are beginning to bite back,” she said.

Scientists continue to scour remote corners of the globe for new antibiotics. Last October, a Norwegian research team was sifting through Arctic mud in the hope of striking medical gold. But new drugs take decades to bring to market, and many potential candidates have failed to reach pharmacies.

Perhaps engineers can help, by giving drug-resistant bacteria nowhere to hide. Technological breakthroughs are helping biomedical researchers to create smart surfaces and diagnostic tools that can help detect infection, and prevent the spread of deadly disease.

Graphene spikes cut bacteria down to size

Vertical graphene flakes form a protective surface that makes it impossible for bacteria to attach. Instead, bacteria are sliced apart by the sharp graphene flakes and killed (Credit: Yen Strandqvist/ Chalmers University of Technology)

Hip replacements and dental implants have become increasingly common, and most surgeries happen without any complications. One of the biggest risks remains that of bacterial infection, but researchers in Sweden think they’ve found a way to handle that.

Their solution relies on a thin layer of graphene flakes that is applied to the surface of an implant. The researchers, from Chalmers University of Technology, were not the first to try graphene, but in the past it had yielded mixed results.

“We discovered that the key parameter is to orient the graphene vertically,” explains Professor Ivan Mijakovic from the university’s department of biology and biological engineering. “If it is horizontal, the bacteria are not harmed.”

In their study, the microscopic graphene flakes faced upwards, like spikes on railings. Human cells are too big to be damaged by these spikes but, for smaller bacteria, they’re like razor wire.

To create the graphene coating, the researchers placed the sample in a vacuum chamber and then heated it to a high temperature as hydrogen, methane and argon were released into the chamber. This process created a thin coating of carbon atoms. To create vertical spikes of graphene, they applied an electric field to the sample in a process known as plasma-enhanced chemical vapour deposition.

Ninja polymers

Some engineers are going for a completely different approach, fighting drug-resistant bacteria on a molecular level. James Hedrick’s work was inspired by an infection acquired after routine knee surgery.

In conjunction with Singapore’s Institute of Bioengineering and Nanotechnology, he and colleagues at IBM have developed a synthetic-molecule polymer that’s designed to kill five deadly kinds of bacteria that are resistant to multiple types of antibiotics. They’ve dubbed their inventions ‘ninja polymers’.

“The mechanism through which these polymers fight bacteria is very different from the way an antibiotic works,” explains Hedrick. “They try to mimic what the immune system does: the polymer attaches to the bacteria’s membrane and then facilitates destabilisation of the membrane. It falls apart, everything falls out and there’s little opportunity for it to develop resistance to these polymers.”

The polymers bind to bacteria and then work their way in, before turning the liquid inside solid. It’s a rather grisly death, but crucially it happens quickly, so the bacteria don’t have time to pass on any resistance.

“As viruses and bacteria contribute to the majority of infectious diseases, this new study rounds out our ability to some day treat a spectrum of infectious diseases with a single, new type of mechanism without the onset of resistance,” says Hedrick.

Needles that turn into 'jelly'

Ryan Donnelly is developing dissolving needles for a better way of giving drugs. Don’t worry, they’re not actually that big (Credit: Queen's University Belfast)

Most antibiotics are given orally – which is undoubtedly more pleasant for patients than the alternatives, but also a major contributor to anti-microbial resistance. “This means that a small quantity of the compound often finds its way into the colon, creating the perfect breeding ground for drug-resistant bacteria,” explains Professor Ryan Donnelly, professor of pharmaceutical technology at Queen’s University Belfast.

“However,” he continues, “it is clearly impractical to expect patients to inject themselves at home, especially considering that more than 20% of people are needle-phobic. Admitting patients to hospital every time they need an antibiotic would quickly bankrupt healthcare providers.”

Donnelly and his team have developed a solution. They have created an antibiotic patch that can painlessly pierce the skin with tiny needles, allowing antibiotics to be gradually absorbed into the blood. The needles turn into a jelly-like material that keeps the holes open, and allows control of the rate at which medicine goes into the skin.

“We hope to show that this unique antibiotic patch prevents resistance development,” says Donnelly. “If we are successful, this approach will significantly extend the lifespan of existing antibiotics, allowing time for development of the next generation of antibiotics. This work has the potential to save many lives.”

Chameleon composites release drugs on demand

Although hospitals and dental surgeries are supposed to be clean, they can also be major breeding grounds for drug-resistant bacteria. Researchers in Saudi Arabia are working on technology to reduce the number of patients who are being infected by bacteria hiding on reusable tools such as X-ray imaging plates, which dentists use for mouth scans.

In the past, smart coatings for such tools have used nano-crystals embedded with silver ions, which have antibacterial properties. But these tend to leach away too rapidly to be of use in a clinical setting.

A team at King Abdullah University of Science and Technology led by associate professor Niveen Khashab has developed a method that uses gold nanoparticles instead.

The team’s approach involves treating gold nanoparticles with bacteria-killing lysozyme enzymes. They are then attached to slightly larger silica nanoparticles that have been stuffed with molecules of antibiotic drugs. This complex cocktail emits a fluorescent red glow in normal, clean conditions. But when bacteria are present, the lysozyme enzyme rips the gold and the silica nano-clusters apart. This simultaneously switches off the fluorescent effect and releases the antibiotic cargo.

The researchers have tested their new polymer in experiments with the bacterium Escherichia coli, and found less leaching than with the silver ion method. They compared X-ray dental plates with and without the smart polymer coating, and found that they could determine the level of bacterial contamination by looking for colour changes under a UV light.

There was no change in the quality of the images obtained using these X-ray plates. “The process of coating is easy,” says Khashab. “We are looking at improving this technology to include other medical devices of different sizes and shapes.”

The future

A number of universities – including University College London, Imperial and Southampton – have long-running projects aimed at tackling the threat of anti-microbial resistance. Engineers from all over the world are focused on tackling the problem – on the large scale, through the ways hospitals and clinics are designed, right through to the nanoscale – and by using smart materials that can kill bacteria on contact.

There won’t just be one solution – tackling this problem means attacking it on all fronts. Doctors and pharmaceutical companies are on the hunt for new antibiotics, and there are some promising possibilities, but they need the efforts of engineers to buy them time.

Content published by Professional Engineering does not necessarily represent the views of the Institution of Mechanical Engineers.